Tabaczar Sabina, Domeradzka Katarzyna, Czepas Jan, Piasecka-Zelga Joanna, Stetkiewicz Jan, Gwoździński Krzysztof, Koceva-Chyła Aneta
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
Nofer Institute of Occupational Medicine, Łódź, Poland.
Pharmacol Rep. 2015 Jun;67(3):527-34. doi: 10.1016/j.pharep.2014.12.010. Epub 2015 Jan 5.
Considering the role of oxidative stress in carcinogenesis, we investigated the effect of synthetic antioxidant Pirolin (3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl) on breast cancer progression. Since the anticancer drugs may cause cardiotoxicity due to oxidative stress in the heart muscle, we also evaluated Pirolin performance in heart tissue and compared its effect with that of the natural dietary flavonoid quercetin.
Sprague-Dawley rats were administered with 7,12-dimethylbenz(a)anthracene (DMBA) and then treated ip with an antioxidant (each at a dose of 10mg/kg b.w.) for 14 days. The histopathology of tumors, their size and multiplicity were assesed. The effect of antioxidants on heart tissue was evaluated by the oxidative stress markers and poly (ADP-ribose) polymerase 1 (PARP 1) cleavage.
The median number of tumors and their volume, at the end of the study, were considerably smaller in both antioxidant-treated groups. We found a better antioxidative performance of quercetin in the heart, since a restoration of the GSH pool and decreased amount of hydroperoxides were observed. Antioxidants did not prevent cardiomyocytes from apoptosis.
The attenuation of tumor progression by Pirolin was comparable with the action of quercetin. No negative changes were observed in the heart of animals after Pirolin treatment. Thus, its use in targeting deregulated redox pathways should be further studied.
考虑到氧化应激在致癌过程中的作用，我们研究了合成抗氧化剂吡咯啉（3-氨基甲酰基-2,2,5,5-四甲基吡咯啉-1-氧基）对乳腺癌进展的影响。由于抗癌药物可能因心肌氧化应激而导致心脏毒性，我们还评估了吡咯啉在心脏组织中的性能，并将其效果与天然膳食类黄酮槲皮素进行了比较。
给Sprague-Dawley大鼠注射7,12-二甲基苯并(a)蒽（DMBA），然后腹腔注射抗氧化剂（每种剂量为10mg/kg体重），持续14天。评估肿瘤的组织病理学、大小和数量。通过氧化应激标志物和聚（ADP-核糖）聚合酶1（PARP 1）裂解来评估抗氧化剂对心脏组织的影响。
在研究结束时，两个抗氧化剂处理组的肿瘤中位数数量及其体积均明显较小。我们发现槲皮素在心脏中的抗氧化性能更好，因为观察到谷胱甘肽池的恢复和氢过氧化物量的减少。抗氧化剂并未阻止心肌细胞凋亡。
吡咯啉对肿瘤进展的抑制作用与槲皮素相当。吡咯啉处理后动物心脏未观察到负面变化。因此，其在靶向失调的氧化还原途径中的应用应进一步研究。
